title: Neonatal stress or morphine treatment alters adult mouse conditioned place preference.
abstract: BACKGROUND
  Hospitalized preterm infants may experience pain and stress, and narcotics are often administered to lessen their suffering. However, prolonged narcotic therapy may be detrimental during neonatal brain development. Using a rat model combining neonatal stress and morphine, we found that neonatal morphine impaired adult learning. Here we describe a new mouse model examining lasting effects of neonatal stress and morphine.
  
  
  OBJECTIVE
  We tested whether repeated neonatal stress and/or morphine exposure affects early neurodevelopmental or adult behaviors.
  
  
  METHODS
  Five groups of C57/BL6 mice (1: untreated; 2: morphine (2 mg/kg s.c., b.i.d.); 3: saline, 4: stress + morphine; 5: stress + saline) were treated from postnatal day (P) 5 to P9. Stress consisted of daily maternal separation/isolation (08:00-15:00 h) with gavage feedings and twice daily exposure to brief hypoxia/hyperoxia. Developmental behaviors included righting (P5) and negative geotaxis (P9). Adult behaviors included elevated plus maze, morphine place-preference conditioning, and forced-swimming. Plasma concentrations of morphine (P7) and corticosterone (P9 and adult) were measured.
  
  
  RESULTS
  Neonatal stress or neonatal morphine alone impaired adult place-preference conditioning, but the combination did not (interaction p < 0.01). Adult basal corticosterones were reduced by neonatal morphine treatment. There were no substantial differences in elevated plus maze or forced-swimming times.
  
  
  CONCLUSIONS
  Neonatal stress and morphine treatment produced long-lasting behavioral and hormonal effects which suggest that neonatal morphine reduces adult arousal and neonatal stress exaggerates adult arousal, each to a degree sufficient to alter learning, while the combined impact of these neonatal treatments does not alter adult learning.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Wash. 98195-6320, USA.
authors.forename: Jared F
authors.initials: JF
authors.lastname: Boasen
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: McPherson
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Hays
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Juul
authors.forename: Christine A
authors.initials: CA
authors.lastname: Gleason
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D018496:Hyperoxia; D000860:Hypoxia; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D003345:Corticosterone